Consumption of a Natural High-Intensity Sweetener Enhances Activity and Expression of Rabbit Intestinal Na+/Glucose Cotransporter 1 (SGLT1) and Improves Colibacillosis-Induced Enteric Disorders.

Andrew W. Moran,Miran A. Al-Rammahi,Catherine Ionescu,Emeline Grand,Kristian Daly,David M. Bravo,Soraya P. Shirazi-Beechey,Emma H. Wall

doi:10.1021/acs.jafc.9b04995

Andrew W. Moran, Miran A. Al-Rammahi + Show 6 more

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https://doi.org/10.1021/acs.jafc.9b04995

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Abstract

Absorption of glucose, via intestinal Na+/glucose cotransporter 1 (SGLT1), activates salt and water absorption and is an effective route for treating Escherichia coli (E. coli)-induced diarrhea. Activity and expression of SGLT1 is regulated by sensing of sugars and artificial/natural sweeteners by the intestinal sweet receptor T1R2-T1R3 expressed in enteroendocrine cells. Diarrhea, caused by the bacterial pathogen E. coli, is the most common post-weaning clinical feature in rabbits, leading to mortality. We demonstrate here that, in rabbits with experimentally E. coli-induced diarrhea, inclusion of a supplement containing stevia leaf extract (SL) in the feed decreases cumulative morbidity, improving clinical signs of disease (p < 0.01). We show that the rabbit intestine expresses T1R2-T1R3. Furthermore, intake of SL enhances activity and expression of SGLT1 and the intestinal capacity to absorb glucose (1.8-fold increase, p < 0.05). Thus, a natural plant extract sweetener can act as an effective feed additive for lessening the negative impact of enteric diseases in animals.

Highlights

Na+/glucose cotransporter 1, SGLT1, is the major route for absorption of glucose across the intestinal brush border membrane
Feeding of low-level antibiotics has been a routine procedure for controlling enteric pathogens, preventing disease and improving health and growth, in particular in post-weaning animals.[24]
Oral rehydration therapy, which relies on absorption of glucose via SGLT1, activating electrolyte and water absorption, is a safe and effective method for the treatment of E. coli- and Vibrio cholerae-induced diarrhea.[1]

Summary

Introduction

Na+/glucose cotransporter 1, SGLT1, is the major route for absorption of glucose across the intestinal brush border membrane. The gut epithelium can sense sugars and artificial sweeteners via the sweet receptor comprising Taste family 1 Receptor 2 (T1R2) and 3 (T1R3) expressed on the luminal membrane of enteroendocrine cells (EEC).[3,4] This results in secretion of gut hormones, glucagon-like peptide 1 (GLP-1), glucagon-like peptide 2 (GLP-2), and glucose-dependent insulinotropic peptide (GIP) from EEC.[5,6] GLP-2 upregulates SGLT1 activity and expression[7,8] in neighboring absorptive enterocytes via a neuro-paracrine pathway.[6,9] GLP-2 increases the villus height and intestinal barrier function,[10,11] thereby promoting gut health These effects have been reported in piglets[12] and calves and ruminants.[13]

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